Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery
Gyorgy G. Ferenczy,
Gyorgy M. Keseru.
Protein kinases are one of the most targeted protein families in current drug discovery pipelines.
They are implicated in many oncological, inflammatory, CNS-related and other clinical indications.
Virtual screening is a computational technique with a diverse set of available tools that has been
shown many times to provide novel starting points for kinase-directed drug discovery. This review
starts with a concise overview of the function, structural features and inhibitory mechanisms of protein
kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings,
we discuss several case studies to illustrate the state of the art in the virtual screening for type I,
type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to
provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors,
as well as a practical tool to anyone who wishes to embark on such an endeavor.
Keywords: Drug discovery, Kinase, Structure-based virtual screening, Inhibitor, Docking, DFG motif, Activation segment,
hinge, Covalent docking.
Rights & PermissionsPrintExport